Dexamethasone selectively attenuates prostanoid-induced vasoconstrictor responses in vitro.
Glucocorticoids bind to specific vascular receptors resulting in a variety of functional consequences that may affect vascular smooth muscle behavior. We, therefore, examined in rabbits the effect of treatment with dexamethasone (2.5 mg/kg) for 6 days on vascular responses to pressor prostanoids in aortic and carotid arterial rings and in the isolated perfused kidney. Isometric tension development to prostaglandin F2 alpha and U46619, a thromboxane/prostaglandin endoperoxide mimetic, was markedly reduced in vessels from dexamethasone-treated rabbits. The inhibitory effect of dexamethasone on vascular reactivity was manifested by an increase in the concentration of agonist for threshold tension development and a reduction in the maximal response to prostaglandin F2 alpha and U46619. In contrast, reactivity to phenylephrine, potassium, histamine, or endothelin was not affected by dexamethasone treatment. In addition, pressor responses to prostaglandin F2 alpha and U46619 in Krebs'-perfused kidneys from dexamethasone-treated rabbits were also diminished. These data suggest that dexamethasone selectively interferes with the expression of receptor-mediated contractile responses to eicosanoids.
Sessa
W C
WC
Department of Pharmacology, New York Medical College, Valhalla 10595.
Nasjletti
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003907:Dexamethasone; D015237:Dinoprost